Biophysical properties optimization

To seek compounds with optimal characteristics for external and internal transfer on a rational basis requires an understanding of pesticide availance and how this is influenced by physico-chemical and biophysical properties to predict the most effective compounds then requires a knowledge of the relationship between these properties and molecular structure. This paper briefly reviews the considerable progress which has been made in these directions and the prospects for future advance. 

In this chapter, we provide an overview of our recent efforts to develop a fundamental science base for the design and preparation of optimal lipid-based carriers of DNA and siRNA for gene therapy and gene silencing. We employ synthesis of custom multivalent lipids, synchrotron X-ray diffraction (XRD) techniques, optical and cryo-electron microscopy, as well as biological assays in order to correlate the structures, chemical, and biophysical properties of cationic liposome (CL)-NA complexes to their biological activity and to clarify the interactions between CL-NA complexes and cellular components. Earlier work has been reviewed elsewhere [1-7] and will not be covered exhaustively here. 

The time-optimal controller proposed here has a firing rate in individual neurons that is maximal during the agonist pulse and independent of eye orientation, while the antagonist muscle is inhibited. We refer to maximal firing in the neuron as the intent of the system, which because of biophysical properties of the neuron membrane, slowly decay over time as described in Enderle (2002). The type of time-optimal controller described here is more complex than the one in 1987 due to physiological considerations. The time-optimal controller operates in two modes, one for small saccades and one for large saccades. 

Empirical energy functions can fulfill the demands required by computational studies of biochemical and biophysical systems. The mathematical equations in empirical energy functions include relatively simple terms to describe the physical interactions that dictate the structure and dynamic properties of biological molecules. In addition, empirical force fields use atomistic models, in which atoms are the smallest particles in the system rather than the electrons and nuclei used in quantum mechanics. These two simplifications allow for the computational speed required to perform the required number of energy calculations on biomolecules in their environments to be attained, and, more important, via the use of properly optimized parameters in the mathematical models the required chemical accuracy can be achieved. The use of empirical energy functions was initially applied to small organic molecules, where it was referred to as molecular mechanics [4], and more recently to biological systems [2,3]. 

The REM, NK and p-spin models all are attempts to capture the important statistical properties of true molecular landscapes in a simple model. Because they contain no biophysical information, they are limited in how well they can achieve this. The block model is an important step in removing some of the simplifications in these models, as it allows for nonstationary properties that can be matched to different regions of molecules. Ideally, landscape models can be based on experimental data. Unfortunately, despite the tremendous interest in molecular optimization, there is still relatively little data that can be used this way. As more data are collected on the effects of substitutions in protein structural and loop regions, antibody CDRs and framework regions, etc., a block or other type of model can be developed that uses appropriate fitness functions for each block. Combined efforts by theoreticians and experimentalists may also help devise experiments that measure key true affinity landscape properties without excessive laboratory effort. 

DNA is a biopolymer that widely exists in the natural world. DNA possesses perfect biophysical and biochemical properties, which have been optimized over billions of years of evolution. These unique properties of DNA offer excellent prospects for serving as a construction material in bioscience. Several attempts have been made to use DNA as a biomaterial. These publications will be summarized in Sect. 5 on biopolymers. 

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